Localized vascular complications associated with catheterization of a vein or artery are common side effects with many medical procedures. Such complications including hemorrhaging of blood vessels, delayed hemostasis time, hematoma, pseudoaneurysm, and arteriovenous (AV) fistula formation can be life threatening. Since cardiac catheterization remains the primary technique for diagnosing coronary artery disease and is used to help delineate coronary anatomy, the information gained is often a medical necessity, despite the risks. Traditionally, the application of pressure to a vein or artery effected by a breach or puncture was the preferred method for reducing complications, however compression of a vein or artery after cardiac catheterization can be very painful for the patients. Compression bandages with weights may be applied for 4-8 hours following hemostasis and patients can be immobilized up to 24 hours. Patients frequently develop back pain and urinary retention in addition to the localized vascular complications.
Two approaches have recently been used to reduce localized vascular complications, namely percutaneous closure/sealant devices and hemostatic patches.
Numerous hemostatic patches have been invented to treat superficial wounds on skin or on the surface of internal organs. These patches are effective at the site where the patch contacts the skin or contacts the surface of an internal organ. Application of the patches in treatment of cardiac catheterization presents a problem in that the underlying puncture in the artery or vein is not directly effected by the active components of the patches. Thus, the vein or artery puncture may continue to bleed after the skin puncture wound is sealed and the possibility of hematoma formation or other localized vascular complications exists. U.S. Pat. No. 6,056,970 discloses a hemostatic biocompatable composition and a method of application wherein the composition is topically maintained in contact with the wound on the skin surface, preferably with light pressure, for a period of time for clotting to occur at the interface between the composition and the wound. A related composition is disclosed in U.S. Pat. No. 6,361,551, where a wound-contacting fabric accelerates clot formation at an interface between a wound surface and the hemostatic fabric. The hemostatic fabric is composed of collagen fibers and can comprise numerous hemostatic agents. U.S. Pat. No. 5,564,849 also discloses a similar patch that accelerates clot formation at an interface between a skin or organ wound surface and the hemostatic patch. The patch comprises active amounts of thrombin and epsilon aminocaproic acid (EACA).
Several compositions that can act as hemostatic agents and typically include collagen or fibrin are known (Falstrom et al., 1997, Catheterization and Cardiovasular Diagnosis 41:79-84; Hoekstra et al., 1998, Biomaterials. 19:1467-1471; Prior et al., 2000, Journal of Biomedical Materials Research. 53(3):252-257). The main disadvantage of such compositions is their limited use in treating breaches or punctures in veins or arteries at a distance. In order to treat breaches or punctures in veins or arteries at a distance beneath the skin surface with such compositions, it is necessary to apply the compositions in an invasive manner so that the compositions are in contact with a breach or puncture in a vein or artery. Since such compositions are effective at the site of contact, topical treatment at a breach or puncture in a vein or artery that is found at some distance from the skin surface is not possible. U.S. Pat. No. 4,394,373 discloses compositions that act as coagulants and may be used to promote clotting of a wound by placing the compositions in contact with the wound where the composition comprises liquid or powder chitosan. U.S. Pat. No. 5,510,102 discloses compositions that act as coagulants and may be used to promote clotting of a wound by placing the compositions in contact with the wound where the composition comprises platelet rich plasma plus a biocompatable polymer that is a hemostatic agent such as alginate. The compositions of U.S. Pat. Nos. 4,394,373 and 5,510,102 are either applied directly to the wound surface, in the case of treatment of a superficial wound or in the case of a puncture in an artery left by a catheterization procedure, the compositions are typically injected into the soft tissue surrounding the arterial puncture site, so that the composition is in contact with the puncture site. The injection of the compositions is an invasive procedure that can lead to complications such as swelling, further damage to blood vessels and tissue, and increased risk of infection.
Hemostatic patches are effective at the interface of the wound and the patch. Thus, in the case of a puncture in a vein or artery caused by catheterization, when a patch causes clotting at the skin surface wound site, the deeper internal puncture in the vein or artery continues to hemorrhage increasing the likelihood that a hematoma or other vascular complications will occur. Hemostatic patches have not been demonstrated to be effective at a distance in treating punctures resulting from catheterization, but nonetheless hemostatic patches have numerous surgical applications where the patches or fabrics can be applied directly to the wound surfaces on organs exposed during surgical procedures.
Another approach to reducing localized vascular complications associated with catheterization procedures has been the development of devices to aid in the application of hemostatic compositions percutaneously, so that a hemostatic composition is administered in contact with the puncture site. Kipshidze et al. (U.S. Pat. No. 5,437,292) and Van Tassel et al. (U.S. Pat. No. 6,193,670 B1) each invented a device for sealing catheter puncture sites in blood vessels. Such a device typically administers a plug composed of collagen or fibrin that extends from the site of the puncture in the vein or artery through the catheter sheath tract to the skin surface. Numerous variations of such device have been developed where the puncture site is sealed with a suture (Wood et al. U.S. Pat. No. 5,746,755), or where the puncture in the blood vessel is sealed from within the blood vessel lumen (Redmond et al. U.S. 2002/0006429 A1). Gwechenberger, Silber, Camenzind, and Sanborn each provided a comparison of sealant devices employed with compression compared with manual compression alone (Camenzind et al, 1994, Journal of the American College of Cardiology. 24(3):655-662; Gwechenberger et al., 1997, Angiology. 48(2):121-126; Sanborn et al., 1993, Journal of the American College of Cardiology. 22(5):1273-1279; Silber et al., 1998, Catheterization and Cardiovasular Diagnosis 43:421-427). Nearly, all commercially available devices and patches are suggested for use in conjunction with compression. The main disadvantage of such devices is the invasive manner in which the compositions or sutures are applied.
Although several hemostatic devices are commercially available, complication rates with theses closure devices are similar to conventional manual compression (Olade et al., 2002, Emedicine Journal, 3(3):1-13). Devices and methods which do not suture the catheter arterial puncture, but plug the catheter tract with collagen from the skin surface to the arterial puncture site have also been shown to be no more effective than manual compression alone (Camenzind et al., 1994, Journal of the American College of Cardiology. 24(3):655-662). Whether arterial puncture closure devices or hemostatic patches are used to treat a breach or puncture in a vein or artery, there remains a need for reducing the incidence of life threatening complications associated with catheterization and other procedures which has been a persistent medical problem which bespeaks the need for new treatments.